Chemokine receptor CXCR3 and its ligands: activity regulation and role in autoinflammatory diseases and juvenile idiopathic arthritis

Three chemokines bind the common G protein-coupled receptor CXCR3 and glycosaminoglycans. In addition, one of these ligands, CXCL11, interacts with atypical chemokine receptor ACKR3. These interactions are crucial for directed migration of inflammatory leukocytes to inflamed tissues. Current literature shows that limited N-terminal modification of chemokine ligands has a significant impact on receptor specificity and biological and inflammatory activity. Data of the guest lab showed that natural C-terminal modifications of CXCR3 ligands also exist. With this PhD thesis we will develop techniques to discriminate between active and inactive ligands. We will study the effects of modifications on ligand receptor interactions, signal transduction and activity of the three chemokine ligands. We will study the activity of CXCR3 and its ligands in different target cells and patients suffering from autoinflammatory diseases and juvenile idiopathic arthritis.